Polyphenolic natural products are of current interest because of their numerous biological activities, and their resulting relevance for human health. Polyphenolic natural products have more than one and often several hydroxyl groups. Several different hydroxylation patterns have been found in nature. Representative examples include: (−)-epiafzelechin, (+)-catechin, (−)-epicatechin, (−)-gallocatechin, (−)-epigallocatechin, their respective 3-gallate esters, as well as two 3-(30-methyl) gallate esters, which are referred to collectively herein as “catechins”. (+)-Catechin, (−)-catechins, (+)-epicatechin and (−)-epicatechin are flavan-3-ols. Catechins are present in the human diet in chocolate, fruits, vegetables and wine, have found use in the treatment of acute coronary syndromes, including but not limited to myocardial infarction and angina; acute ischemic events in other organs and tissues, including but not limited to renal injury, renal ischemia and diseases of the aorta and its branches; injuries arising from medical interventions, including but not limited to coronary artery bypass grafting (CABG) procedures and aneurysm repair; cancer; and metabolic diseases, including but not limited to diabetes mellitus. Health benefits of catechins have been broadly attributed to their antioxidant and mitochondria biogenesis properties, effects on intestinal microorganisms and nutrient absorption, and effects on metabolism and metabolic enzymes.
Catechins for use as pharmaceutical and nutraceutical preparations have been obtained through plant extraction, followed if desired by purification of individual catechin species using chromatographic methods. However, often the availability of various purified catechins from natural sources is very limited and expensive. Also the current processes, particularly for the synthesis of epicatechin of desired stereochemistry, either involve very expensive starting materials and/or reagents, or are synthetically challenging and not amenable for larger scale synthesis.
Certain processes for synthesis of epicatechin are available in prior art. One such process is disclosed in PCT/IN2012/000052. The present invention involves novel intermediates and is amenable to commercial scale-up. Hence, it is an objective to provide an efficient and cost effective synthetic method for the synthesis of cis-catechin/epicatechin and its intermediates in their enatiomerically pure or enatiomerically enriched forms.